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INFLAMMATION  AND  DISEASES

 

AN OVERVIEW OF INFLAMMATION: MECHANISM AND CONSEQUENCES

Inflammation is an essential response provided by the immune systems that ensures the survival during infection and tissue injury. Inflammatory responses are essential for the maintenance of normal tissue homeostasis. The molecular mechanism of inflammation is quite a complicated process which is initiated by the recognition of specific molecular patterns associated with either infection or tissue injury. The entire process of the inflammatory response is mediated by several key regulators involved in the selective expression of proinflammatory molecules. Prolonged inflammations are often associated with severe detrimental side effects on health. Alterations in inflammatory responses due to persistent inducers or genetic variations are on the rise over the last couple of decades, causing a variety of inflammatory diseases and pathophysiological conditions.

Afsar U. Ahmed - Front Biol 2011, 6(4):274-81


THE IMMUNOPATHOLOGY OF SEPSIS AND POTENTIAL THERAPEUTIC TARGETS

Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. In sepsis, the immune response that is initiated by an invading pathogen fails to return to homeostasis, thus culminating in a pathological syndrome that is characterized by sustained excessive inflammation and immune suppression. Our understanding of the key mechanisms involved in the pathogenesis of sepsis has increased tremendously, yet this still needs to be translated into novel targeted therapeutic strategies. Pivotal for the clinical development of new sepsis therapies is the selection of patients on the basis of biomarkers and/or functional defects that provide specific insights into the expression or activity of the therapeutic target.

Tom van der Poll et al. - Nat Rev Immunol 2017, 17(7):407-20.


NATIONAL INPATIENT HOSPITAL COSTS: THE MOST EXPENSIVE CONDITIONS BY PAYER, 2013

Septicemia was the most expensive condition treated, accounting for $23.7 billion, or 6.2 percent of the aggregate costs for all hospitalizations. Other high-cost hospitalizations were for osteoarthritis ($16.5 billion, or 4.3 percent), liveborn (newborn) infants ($13.3 billion, or 3.5 percent), complication of device, implant or graft ($12.4 billion, or 3.3 percent), and acute myocardial infarction ($12.1 billion, or 3.2 percent).

Celeste M. Torio and Brian J. Moore - HCUP Statistical Brief #204, 2016


​MULTIPLE SCLEROSIS: IMMUNOPATHOLOGY AND TREATMENT UPDATE

The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include -interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS.

Narges Dargahi et al. - Brain Sci 2017, 7, 78


ECONOMICS AND COST-EFFECTIVENESS OF MULTIPLE SCLEROSIS THERAPIES IN THE USA

Multiple sclerosis (MS) is a disabling, chronic disease that imposes a significant economic burden on patients and the US healthcare system. The largest cost component for individuals with MS are prescription drugs, specifically disease-modifying therapies (DMTs). Despite an increase in the number and diversity of DMTs over the past 10 years, acquisition costs for all DMTs have escalated dramatically at rates substantially higher than medical inflation. Currently, costs for most DMTs exceed $70,000 a year. Recent cost-effectiveness studies suggest the cost for nearly all DMTs exceeds generally accepted thresholds for what is considered a good value in the USA, even after factoring expected rebates. The high cost of DMTs is symptomatic of systemic dysfunction in the pharmaceutical market. Strategies aimed at reigning in high-cost medications include proposals ranging from increasing pricing transparency to allowing Medicare to negotiate directly with manufacturers. Because the economics of pharmaceuticals are inherently complex, a diversity of approaches will be required.

Daniel M Hartung - Neurotherapeutics, DOI 10.1007/s13311-017-0566-3


THE IMMUNOPATHOGENESIS OF SEROPOSITIVE RHEUMATOID ARTHRITIS: FROM TRIGGERING TO TARGETING

Patients with rheumatoid arthritis can be divided into two major subsets characterized by the presence versus absence of antibodies to citrullinated protein antigens (ACPAs) and of rheumatoid factor (RF). The antibody-positive subset of disease, also known as seropositive rheumatoid arthritis, constitutes approximately two-thirds of all cases of rheumatoid arthritis and generally has a more severe disease course. ACPAs and RF are often present in the blood long before any signs of joint inflammation, which suggests that the triggering of autoimmunity may occur at sites other than the joints (for example, in the lung). This Review summarizes recent progress in our understanding of this gradual disease development in seropositive patients. We also emphasize the implications of this new understanding for the development of preventive and therapeutic strategies. Similar temporal and spatial separation of immune triggering and clinical manifestations, with novel opportunities for early intervention, may also occur in other immune-mediated diseases.

Vivianne Malmström et al. - Nat Rev Immunol 2017, 17(1):60-75


COMPARING BIOLOGIC COST PER TREATED PATIENT ACROSS INDICATIONS AMONG ADULT US MANAGED CARE PATIENTS: A RETROSPECTIVE COHORT STUDY

Our objective was to estimate biologic costs and treatment patterns in US managed care patients with rheumatoid arthritis, psoriatic arthritis, psoriasis, and/or ankylosing spondylitis ... Most of the 24,460 patients received etanercept (48 %), adalimumab (29 %), or infliximab (12 %) as the index biologic. On the index date, 44 % were new to biologic therapy and 56 % were continuing biologic therapy. Biologic cost per treated patient for 1 year was as follows: etanercept $US24,859, adalimumab $US26,537, and infliximab $US26,468.

Tao Gu et al. - Drugs Real World Outcomes 2016, 3(4):369-81